Rapid Administration Pilot for Infusing Dinutuximab

Summary

Dinutuximab is an immunotherapy that has greatly improved outcomes for children with high-risk neuroblastoma and is now a standard part of treatment for both newly diagnosed and relapsed disease. However, the medication is typically given through an intravenous (IV) infusion over 10-20 hours a day for four consecutive days, requiring prolonged hospital stays that place a significant burden on children, families, and healthcare resources. Earlier studies of dinutuximab, as well as experience with a similar immunotherapy, suggest that these medications can be safely given over a much shorter period of time. This study is evaluating whether children with high-risk neuroblastoma can safely receive dinutuximab over five hours or less. Early results have been encouraging. The first group of patients successfully received most treatments with dinutuximab in about two hours. Children experienced very low pain levels and required approximately 78% less opioid pain medication compared with the traditional longer infusion. Several patients were able to receive treatment as outpatients without requiring hospital admission, while hospitalizations that did occur were primarily related to chemotherapy or other non-medical reasons rather than the rapid infusion itself. The study is now expanded to further evaluate the safety of rapid infusion across multiple treatment cycles at different centers in the United States. Researchers will also examine how the drug is processed by the body, whether the immune system develops antibodies against the treatment, and whether the faster infusion continues to reduce the need for opioid pain medication. In addition, children and their caregivers will complete questionnaires about symptoms and treatment experiences to better understand the impact of the faster dinutuximab infusion on quality of life and the overall treatment experience.

Timeline

Start

2022-11-29

Primary completion

2028-11

Completion

2029-11

Publications

• Background Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, Shimada H, Grupp SA, Seeger R, Reynolds CP, Buxton A, Reisfeld RA, Gillies SD, Cohn SL, Maris JM, Sondel PM; Children's Oncology Group. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010 Sep 30;363(14):1324-34. doi: 10.1056/NEJMoa0911123.
• Background Yu AL, Gilman AL, Ozkaynak MF, Naranjo A, Diccianni MB, Gan J, Hank JA, Batova A, London WB, Tenney SC, Smith M, Shulkin BL, Parisi M, Matthay KK, Cohn SL, Maris JM, Bagatell R, Park JR, Sondel PM. Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032. Clin Cancer Res. 2021 Apr 15;27(8):2179-2189. doi: 10.1158/1078-0432.CCR-20-3909. Epub 2021 Jan 27.
• Background Mody R, Naranjo A, Van Ryn C, Yu AL, London WB, Shulkin BL, Parisi MT, Servaes SE, Diccianni MB, Sondel PM, Bender JG, Maris JM, Park JR, Bagatell R. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial. Lancet Oncol. 2017 Jul;18(7):946-957. doi: 10.1016/S1470-2045(17)30355-8. Epub 2017 May 23.
• Background Desai AV, Fox E, Smith LM, Lim AP, Maris JM, Balis FM. Pharmacokinetics of the chimeric anti-GD2 antibody, ch14.18, in children with high-risk neuroblastoma. Cancer Chemother Pharmacol. 2014 Nov;74(5):1047-55. doi: 10.1007/s00280-014-2575-9. Epub 2014 Sep 12.
• Background Marachelian A, Desai A, Balis F, Katzenstein H, Qayed M, Armstrong M, Neville KA, Cohn SL, Bush M, Gunawan R, Lim AP, Smith MA, Smith LM. Comparative pharmacokinetics, safety, and tolerability of two sources of ch14.18 in pediatric patients with high-risk neuroblastoma following myeloablative therapy. Cancer Chemother Pharmacol. 2016 Feb;77(2):405-12. doi: 10.1007/s00280-015-2955-9. Epub 2016 Jan 20.
• Background Mody R, Yu AL, Naranjo A, Zhang FF, London WB, Shulkin BL, Parisi MT, Servaes SE, Diccianni MB, Hank JA, Felder M, Birstler J, Sondel PM, Asgharzadeh S, Glade-Bender J, Katzenstein H, Maris JM, Park JR, Bagatell R. Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group. J Clin Oncol. 2020 Jul 1;38(19):2160-2169. doi: 10.1200/JCO.20.00203. Epub 2020 Apr 28.

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Indications